Morphine induces the apoptosis of mouse hippocampal neurons HT-22 through upregulating miR-181-5p

Y.-L. Wang, X.-H. An, X.-Q. Zhang, J.-H. Liu, J.-W. Wang, Z.-Y. Yang

Department of Anesthesiology, International Peace Maternity and Child Health Hospital, Shanghai JiaoTong University School of Medicine, Shanghai Key Laboratory of Embryo Original Disease, Shanghai Municipal Key Clinical Specialty, Shanghai, China. yankylge@aliyun.com

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• Pharmacology

OBJECTIVE: To elucidate the role of morphine in inducing apoptosis of mouse hippocampal neurons HT-22 by upregulating microRNA-181-5p (miR-181-5p).

MATERIALS AND METHODS: After treatment of different doses of morphine, changes in proliferative ability, apoptosis, and expression levels of miR-181-5p and MAPK1 in HT-22 cells were assessed through a series of functional experiments. Regulatory effects of miR-181-5p on morphine-induced phenotype changes of HT-22 cells were examined. The interaction between miR-181-5p and MAPK1, and their involvement in morphine-induced neuron apoptosis were explored by Luciferase assay and rescue experiments, respectively.

RESULTS: Morphine treatment markedly attenuated viability and proliferative ability in HT-22 cells, while apoptotic rate increased. MiR-181-5p was upregulated and MAPK1 was downregulated in HT-22 cells by morphine induction. Knockdown of miR-181-5p enhanced viability and proliferative ability, as well as reduced apoptosis in morphine-induced HT-22 cells. MiR-181-5p could specifically bind MAPK1 and negatively regulate its expression level. Knockdown of MAPK1 was able to reverse the regulatory effects of miR-181-5p on morphine-induced phenotype changes of HT-22 cells.

CONCLUSIONS: Morphine induces apoptosis of hippocampal neurons HT-22 by upregulating miR-181-5p to suppress the level of MAPK1.

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